Schematic Diagram of Malignant Melanoma

Predisposing Factors

Precipitating Factors

Age : below 30 and above 50 Sex: male Race: European American Family History Blond red hair Hereditary Skin with giant congenital nevi: Large and irregular moles Burn scars Tendency to develop freckles Fair skin, light hair, and light-colored eyes Many (more than 100) moles History of x-ray therapy, exposure to certain chemical agents

Intense, intermittent sun exposure

Exposure to UV lights or artificial lightings

Increase enzymatic activity within the melanosomes

Melanocytes produces melanin from amino acid tyrosine with the help of tyrosinase in the organelle melanosomes.

Dispersion of melanin to keratinocytes

Melanin granules cluster to form a protective veil over the cells on the side toward the skin surface

Darkening of the skin Sunburns

Recurrent exposure to UV lights

1UVA rays penetrates the dermis,

UVB rays penetrates the epidermis

1oxidative stress occur Direct damage on the DNA bases of epidermal cells Increased production of oxygen free radicals

Accumulation of free radicals acts as cocarcinogen Disruption of collagen and fibers in the extracellular matrix

Destruction of melanocytes and Langerhans cells

Decreased ability of the skin cells to eliminate the dead cells that has a potential for malignancy

Decreased ability of the skin cells to identify and repair DNA

Failure of the DNA repair

Mutations in cell genes

activation of growth promoting oncogenes

activation of apoptosis controlling

genes

activation of growth suppressing anti oncogenes

Unregulated cell growth and differentiation

Occurrence of radial growth phase in the epidermis

Formation of dysplastic nevus

vertical growth phase occur

Marked focal deep penetration of atypical melanocytes into the dermis and subcutaneous tissue

Appearance of round flat jet black spot

loss of cohesiveness and adhesion

elaboration of degrative
enzymes

alterations in contact
inhibition

expression of altered
tissue antigens

impaired cell to cell

communication

permits shedding of tumors surface cells

synthesis and secretions of enzyme that breakdown proteins involved in cell to cell cohesion

cancer cells grow rampantly without regard to other tissue

production of

immunologically
foreign antigens

interference with formation of intracellular connections and responsiveness to membrane derived signals

Malignant melanoma

Tumor emboli enter the lymph channels by way of the interstitial fluid

malignant cells lodge in lymph nodes

Attachment of malignant cells to endothelium

Endothelium retracts allowing the malignant cells to enter the basement and secrete lysosomal enzymes

Destruction of surrounding tissues and thereby allowing implantation

Micrometastasis of malignant cells